Neurofibromatoses (NF) are genetic disorders of the nervous system. NF comprises three types of disease: Neurofibromatosis 1 (NF-1), Neurofibromatosis 2 (NF-2), and Schwannomatosis. They all have different genetic origins. However, they have a common feature: the development of tumors of the nervous system, particularly of the nerve sheath cell known as a Schwann cell. NF-1 is characterized by the development of neurofibromas associated with peripheral nerves. These benign tumors consist of various cell types, namely a mixture of Schwann cells, perennial fibroblasts and mast cells. The frequency of occurrence is 1 in 3000 persons. The second type, NF2, can be diagnosed by the presence of bilateral vestibular schwannomas, but schwannomas on other cranial and spinal nerves, and meningiomas and ependynomas occur as well. Schwannomas are also benign tumors, but consist only of Schwann cells. The frequency of occurrence is 1 in 25,000 persons. The third type of NF is Schwannomatosis, which presents with multiple schwannomas, but not involving the vestibular branch of the auditory nerve. A common and unique feature of this type of NF is severe unrelenting pain. The frequency of occurrence is 1 in 40,000 persons. As a result, NF patients can suffer learning disabilities, hearing loss, imbalance, blindness, deformation, pain and higher mortality. Currently, there are no known approved drug therapies for the treatment of NF.
In NF1 and NF2, there is a defect in tumor suppressor proteins, neurofibromin and merlin, respectively. One genetic mutation, INI1, also called SMARCB2 has been associated with Schwannomatosis. Consequently, abnormal Schwann cells present altered proliferation patterns, survival and cell morphology that lead to tumor formation. Normal Schwann cells undergo continuous morphological changes as they develop into myelinating cells. These changes are orchestrated by extracellular signals arising from the axon and basal lamina. To date, there are limited treatments for NF, and these possess drawbacks.